The long range purpose of this project is to study the immunologic, biochemical, and molecular genetic aspects of the factor VIII/von Willebrand factor protein. We have initiated studies to identify fragments of vWf which can act as antithrombotic agents. These fragments of vWf are in the Val449-Ser728 of the plasma protein. Identification of a recombinant fragment of vWf Met504-Lys728 inhibits plasma and platelet vWf binding to GPlb, heparin, and GPIIbLIIIa. The topics of present interest are: 1) the defects of the von Willebrand factor protein in von Willebrand's disease; 2) the importance of carbohydrate content in biological functions; 3) the relationship of carbohydrate content to atherosclerosis; 4) the mechanism of thrombin activation; and 5) biochemical characterization of the biologically active sites of the factor VIII/von Willebrand factor proteins. Recent studies of the platelet von Willebrand factor isolated from human platelets reveal significant differences from its plasma counterpart.